RESUMO
Reduced nicotinamide adenine dinucleotide (NADH)-detecting electrochemical sensors are attractive in monitoring and diagnosing various physiological disorders of NADH abnormalities. The NADH detection methods using conventional electrodes are challenging due to slow electron transfer and fouling effect. Interestingly, paper-based flexible and disposable electrodes (PE) are superior for sensing biomolecules through simple detection procedures with excellent sensitivity and selectivity. Herein, to construct a conducting polypeptide-modified paper electrode, initially, polytyrosine (PTyr) is synthesized from l-tyrosine N-carboxy anhydride through ring-opening polymerization, and PTyr is drop-coated on the PE. The PTyr-modified paper electrode (PMPE) demonstrated excellent electrochemical properties and facilitated the electrooxidation of NADH at a lower potential of 576 mV. The PMPE displayed a linear detection between 25 and 145 µM of NADH concentration, with a lower detection limit of 0.340 µM. Under ideal circumstances, the sensor developed displayed an excellent NADH detection capability without interference with the most common electroactive species, ascorbic acid. The PMPE facilitates good electrocatalytic activity toward NADH, which can also be employed as a substrate material for biofuel cells.
Assuntos
Eletrodos , NAD , Papel , NAD/análise , NAD/química , Peptídeos/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Oxirredução , Limite de Detecção , Técnicas Biossensoriais/métodosRESUMO
Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts.
Assuntos
Cardiopatias Congênitas , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Humanos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Criança , Big Data , Imageamento por Ressonância Magnética , Projetos de Pesquisa , Fatores Etários , Adolescente , Pré-EscolarRESUMO
BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.
Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Miocardite/diagnóstico por imagem , Miocardite/fisiopatologia , Adolescente , Criança , Eletrocardiografia/métodos , Feminino , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Miocardite/sangue , Miocardite/etiologia , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Inositol phosphates are widely produced throughout animal and plant tissues. Diphosphoinositol pentakisphosphate (InsP7) contains an energetic pyrophosphate bond. Here we demonstrate that disruption of inositol hexakisphosphate kinase 1 (InsP6K1), one of the three mammalian inositol hexakisphosphate kinases (InsP6Ks) that convert inositol hexakisphosphate (InsP6) to InsP7, conferred enhanced phosphatidylinositol-(3,4,5)-trisphosphate (PtdIns(3,4,5)P3)-mediated membrane translocation of the pleckstrin homology domain of the kinase Akt and thus augmented downstream PtdIns(3,4,5)P3 signaling in mouse neutrophils. Consequently, these neutrophils had greater phagocytic and bactericidal ability and amplified NADPH oxidase-mediated production of superoxide. These phenotypes were replicated in human primary neutrophils with pharmacologically inhibited InsP6Ks. In contrast, an increase in intracellular InsP7 blocked chemoattractant-elicited translocation of the pleckstrin homology domain to the membrane and substantially suppressed PtdIns(3,4,5)P3-mediated cellular events in neutrophils. Our findings establish a role for InsP7 in signal transduction and provide a mechanism for modulating PtdIns(3,4,5)P3 signaling in neutrophils.
Assuntos
Fosfatos de Inositol/imunologia , Neutrófilos/imunologia , Fosfatos de Fosfatidilinositol/imunologia , Fosfotransferases (Aceptor do Grupo Fosfato)/antagonistas & inibidores , Animais , Dimetil Sulfóxido/farmacologia , Células HL-60 , Humanos , Imunidade Inata/imunologia , Isoenzimas , Camundongos , Camundongos Knockout , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Fagocitose/imunologia , Fosfotransferases (Aceptor do Grupo Fosfato)/genética , Fosfotransferases (Aceptor do Grupo Fosfato)/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de SinaisRESUMO
Peptide-based polymers are evolving as promising materials for various biomedical applications. Among peptide-based polymers, polytyrosine (PTyr)-based and l-tyrosine (Tyr)-derived polymers are unique, due to their excellent biocompatibility, degradability, and functional as well as engineering properties. To date, different polymerization techniques (ring-opening polymerization, enzymatic polymerization, condensation polymerization, solution-interfacial polymerization, and electropolymerization) have been used to synthesize various PTyr-based and Tyr-derived polymers. Even though the synthesis starts from Tyr, different synthesis routes yield different polymers (polypeptides, polyarylates, polyurethanes, polycarbonates, polyiminocarbonate, and polyphosphates) with unique functional characteristics, and these polymers have been successfully used for various biomedical applications in the past decades. This Review comprehensively describes the synthesis approaches, classification, and properties of various PTyr-based and Tyr-derived polymers employed in drug delivery, tissue engineering, and biosensing applications.
Assuntos
Polímeros , Tirosina , Polímeros/química , Tirosina/química , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Peptídeos , PolimerizaçãoRESUMO
Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection.
Assuntos
COVID-19 , Cardiopatias , Imageamento por Ressonância Magnética , Humanos , COVID-19/complicações , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Espectroscopia de Ressonância Magnética , Miocardite/diagnóstico por imagem , Valor Preditivo dos Testes , Cardiopatias/diagnóstico por imagem , Cardiopatias/etiologiaRESUMO
To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.
Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Humanos , SARS-CoV-2 , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Volume Sistólico , Função Ventricular Esquerda , Síndrome de Resposta Inflamatória Sistêmica , Sistema de RegistrosRESUMO
Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.
Assuntos
COVID-19 , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Criança , Humanos , COVID-19/complicações , COVID-19/virologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/virologiaRESUMO
BACKGROUND: Recent evidence shows an association between coronavirus disease 2019 (COVID-19) infection and a severe inflammatory syndrome in children. Cardiovascular magnetic resonance (CMR) data about myocardial injury in children are limited to small cohorts. The aim of this multicenter, international registry is to describe clinical and cardiac characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 using CMR so as to better understand the real extent of myocardial damage in this vulnerable cohort. METHODS AND RESULTS: Hundred-eleven patients meeting the World Health Organization criteria for MIS-C associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having clinical cardiac involvement and having received CMR imaging scan were included from 17 centers. Median age at disease onset was 10.0 years (IQR 7.0-13.8). The majority of children had COVID-19 serology positive (98%) with 27% of children still having both, positive serology and polymerase chain reaction (PCR). CMR was performed at a median of 28 days (19-47) after onset of symptoms. Twenty out of 111 (18%) patients had CMR criteria for acute myocarditis (as defined by the Lake Louise Criteria) with 18/20 showing subepicardial late gadolinium enhancement (LGE). CMR myocarditis was significantly associated with New York Heart Association class IV (p = 0.005, OR 6.56 (95%-CI 1.87-23.00)) and the need for mechanical support (p = 0.039, OR 4.98 (95%-CI 1.18-21.02)). At discharge, 11/111 (10%) patients still had left ventricular systolic dysfunction. CONCLUSION: No CMR evidence of myocardial damage was found in most of our MIS-C cohort. Nevertheless, acute myocarditis is a possible manifestation of MIS-C associated with SARS-CoV-2 with CMR evidence of myocardial necrosis in 18% of our cohort. CMR may be an important diagnostic tool to identify a subset of patients at risk for cardiac sequelae and more prone to myocardial damage. CLINICAL TRIAL REGISTRATION: The study has been registered on ClinicalTrials.gov, Identifier NCT04455347, registered on 01/07/2020, retrospectively registered.
Assuntos
COVID-19 , Miocardite , COVID-19/complicações , Criança , Meios de Contraste , Gadolínio , Humanos , Espectroscopia de Ressonância Magnética , Miocardite/diagnóstico por imagem , Miocardite/epidemiologia , Valor Preditivo dos Testes , Sistema de Registros , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
Quorum sensing mediated biofilm formation has a major role in modern therapeutics due to adherence of cells on the solid surface. Here, we have developed a stable polyurethane blend with a 6-methylcoumarin (6-MC) composite that showed significant antibiofilm activity. The 6-MC was found to prominently inhibit P. aeruginosa PAO1 biofilm formation at 125 µg/ml and was able to inhibit various virulence factors such as pyocyanin, siderophore, exopolysaccharide, elastase and proteases, including motility of the bacteria. In addition, 6-MC was found functionally active in saving the C. elegans from P. aeruginosa PAO1 infection. Moreover, docking studies of different activator proteins correlate well with in vitro and in vivo results. To enhance this biological activity, 6-MC was blended with polyurethane, which also revealed superior antibiofilm activity on plastic and glass surfaces compared to a polyurethane coating. Therefore, the 6-MC could be used to combat P. aeruginosa infection for effective treatment and antibiofilm applications on solid surfaces through polyurethane blending and subsequent film fabrication strategies. KEY POINTS: ⢠6-Methylcoumarin significantly inhibits P. aeruginosa PAO1 biofilm ⢠6-MC was found functionally active in saving the C. elegans from PAO1 infection ⢠6-MC and polyurethane blend showed superior antibiofilm activity.
Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Animais , Antibacterianos/farmacologia , Biofilmes , Caenorhabditis elegans , Cumarínicos , Poliuretanos , Fatores de VirulênciaRESUMO
In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was "indicated." Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2-25% for RL 5, and 0-5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.
Assuntos
Fidelidade a Diretrizes , Síndrome de Linfonodos Mucocutâneos/terapia , Tromboembolia Venosa/prevenção & controle , Adolescente , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Criança , Aneurisma Coronário/etiologia , Aneurisma Coronário/terapia , Feminino , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Sistema de Registros , Estudos Retrospectivos , Varfarina/administração & dosagemRESUMO
OPINION STATEMENT: Assessing the quality of health care delivered is a priority across medical specialties, but it is particularly critical for radiation oncology, a field with rapid introduction of new technologies and treatment paradigms. Deviation from acceptable standards can lead to delivery of inferior therapies and medical errors that can directly compromise patient clinical outcome, thus leading to disparities in quality of care. Professional oncologic specialty societies often take ownership of standardizing best practices by issuing evidence-based disease-specific consensus guidelines. They also inform quality indicators that are set as requirements for accreditation, maintenance of certification, and reimbursement. Cooperative groups also create benchmarks for quality radiation therapy through design of clinical protocols that set standard-of-care treatment practices. Pelvic radiotherapy for colorectal and anal cancers has undergone a significant transformation in radiation planning and delivery including increased complexity in contour segmentation with a transition from three-dimensional to intensity-modulated radiation therapy (IMRT). Compliance with quality metrics proposed in national consensus guidelines and participation in clinical trials help keep practicing radiation oncologists up-to-date with advances in our field and well-trained to provide safe and effective high-value care.
Assuntos
Neoplasias do Ânus/radioterapia , Neoplasias do Colo/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Pelve/efeitos da radiação , Controle de Qualidade , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used to diagnose myocarditis in adults but its use in children is not well-established. We sought to describe the presentation, CMR protocol and findings, and outcomes in a multicenter cohort of children with myocarditis. METHODS: Thirteen hospitals retrospectively identified patients meeting the following inclusion criteria: 1) diagnosis of myocarditis by the managing physicians, 2) age <21 years, 3) CMR examination within 30 days of presentation, and 4) no congenital heart disease. Clinical data and test results, including CMR findings, were abstracted from the medical record. RESULTS: For the 143 patients meeting inclusion criteria, the median age was 16.0 years (range, 0.1-20.3) and 139 (97 %) were hospitalized at the time of CMR. The median time from presentation to CMR was 2 days (0-28). The median left ventricular ejection fraction at CMR was 56 % (10-74), with 29 (20 %) below 45 %. The median right ventricular ejection fraction was 54 % (15-72), with 11 (8 %) below 40 %. There was significant variability among centers in the types of tissue characterization techniques employed (p < 0.001). Overall, late gadolinium enhancement (LGE) was used in 100 % of studies, followed by T2-weighted imaging (T2W) in 69 %, first-pass contrast perfusion (FPP) in 48 %, and early gadolinium enhancement (EGE) in 28 %. Abnormalities were most common with LGE (81 %), followed by T2W (74 %), EGE (55 %), and FPP (8 %). The CMR study was interpreted as positive for myocarditis in 117 patients (82 %), negative in 18 (13 %), and equivocal in 7 (5 %), yielding a sensitivity of 82 %. At a median follow-up of 7.1 months (0-87), all patients were alive and 5 had undergone cardiac transplantation. CMR parameters at presentation associated with persistent left ventricular dysfunction were larger left ventricular end-diastolic volume and lower left and right ventricular ejection fraction but not abnormal LGE. CONCLUSIONS: Despite significant practice variation in imaging protocol among centers, CMR had a high sensitivity for the diagnosis of myocarditis in pediatric patients. Abnormalities were most often seen with LGE followed by T2W, EGE, and FPP. These findings should be useful in designing future prospective studies.
Assuntos
Imageamento por Ressonância Magnética , Miocardite/diagnóstico , Miocárdio/patologia , Volume Sistólico , Função Ventricular Esquerda , Função Ventricular Direita , Adolescente , Fatores Etários , Criança , Pré-Escolar , Meios de Contraste , Transplante de Coração , Hospitalização , Humanos , Lactente , Miocardite/patologia , Miocardite/fisiopatologia , Miocardite/cirurgia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To identify genes that both modulate beta-catenin activity and are essential for colon cancer cell proliferation, we conducted two loss-of-function screens in human colon cancer cells and compared genes identified in these screens with an analysis of copy number alterations in colon cancer specimens. One of these genes, CDK8, which encodes a member of the mediator complex, is located at 13q12.13, a region of recurrent copy number gain in a substantial fraction of colon cancers. Here we show that the suppression of CDK8 expression inhibits proliferation in colon cancer cells characterized by high levels of CDK8 and beta-catenin hyperactivity. CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer a clinical benefit in beta-catenin-driven malignancies.
Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Regulação Neoplásica da Expressão Gênica , Oncogenes , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , Neoplasias Colorretais/patologia , Quinase 8 Dependente de Ciclina , Quinases Ciclina-Dependentes/deficiência , Dosagem de Genes , Humanos , Proteínas Oncogênicas/deficiência , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Interferência de RNA , Transcrição GênicaRESUMO
Xp11 translocation renal cell carcinoma (XPTRCC) is a very rare kidney neoplasm, which has been predominantly reported in young patients. Sarcomatoid transformation in renal cell carcinomas is known. However, its occurrence in XPTRCC is unreported so far in the literature. We report a unique case of sarcomatoid transformation in a XPTRCC in a 23-year-old female, who presented with a huge right-sided renal mass and had metastatic deposits in lungs. Morphologically, clear cell morphology with papillary architecture along with foci of sarcomatoid transformation and rhabdoid differentiation were noted. Immunohistochemistry showed Pax-8 and TFE-3 expression in all components including the sarcomatous areas, whereas CK and EMA were expressed in conventional clear cell component. We present an extremely rare case of sarcomatous transformation in XPTRCC and discuss the case as determined by histopathology and immunocytochemistry. To our knowledge, this is the first case of sarcomatoid transformation XPTRCC being reported in the world literature.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Sarcoma , Adulto , Humanos , Feminino , Adulto Jovem , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Rim/patologia , Diferenciação Celular , Translocação GenéticaRESUMO
BACKGROUND: Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection. METHODS: The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities. CONCLUSIONS: There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.
Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Síndrome de Resposta Inflamatória Sistêmica , Criança , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/terapia , Sistema de RegistrosRESUMO
Evidence from medicine and other fields has shown that gender diversity results in better decision making and outcomes. The incoming workforce of congenital heart specialists (especially in pediatric cardiology) appears to be more gender balanced, but past studies have shown many inequities. Gender-associated differences in leadership positions, opportunities presented for academic advancement, and recognition for academic contributions to the field persist. In addition, compensation packages remain disparate if evaluated based on gender with equivalent experience and expertise. This review explores these inequities and has suggested individual and institutional changes that could be made to recruit and retain women, monitor the climate of the institution, and identify and eliminate bias in areas like salary and promotions.
Assuntos
Equidade de Gênero , Cardiopatias Congênitas , Médicas , Humanos , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/terapia , Feminino , Médicas/estatística & dados numéricos , Médicas/tendências , Masculino , Liderança , Cardiologia/tendências , Pediatria/tendências , Salários e Benefícios , Sexismo/tendências , Fatores Sexuais , Cardiologistas/tendênciasRESUMO
Vascular malformations are anomalies that are caused by disturbances in vasculogenesis. Depending upon the dominant structure present histologically, they may be found in different combinations of vascular elements and are named hemangiolymphangioma (HLA) or lymphangiohemangioma (LHA). HLA occurs in multiple anatomical sites, such as the head and neck, axilla, abdominal cavity, extremities, and urinary bladder, but it is infrequent in the oral cavity. An 18-year-old male with a history of abdominal tuberculosis presented with an asymptomatic mandibular gingival swelling that was histologically diagnosed as HLA. A six-month follow-up revealed no recurrence. The observations reported in this case are unusual, and our literature review revealed no previously documented case of gingival HLA.
RESUMO
Purpose: The aim of this research is to investigate the factors that facilitate the adoption of artificial intelligence (AI) in order to establish effective human resource management (HRM) practices within the Indian pharmaceutical sector. Design/methodology/approach: A model explaining the antecedents of AI adoption for building effective HRM practices in the Indian pharmaceutical sector is proposed in this study. The proposed model is based on task-technology fit theory. To test the model, a two-step procedure, known as partial least squares structural equational modeling (PLS-SEM), was used. To collect data, 160 HRM employees from pharmacy firms from pan India were approached. Only senior and specialized HRM positions were sought. Findings: An examination of the relevant literature reveals factors such as how prepared an organization is, how people perceive the benefits, and how technological readiness influences AI adoption. As a result, HR systems may become more efficient. The PLS-SEM data support all the mediation hypothesized by proving both full and partial mediation, demonstrating the accuracy of the proposed model. Originality: There has been little prior research on the topic; this study adds a great deal to our understanding of what motivates human resource departments to adopt AI in the pharmaceutical companies of India. Furthermore, AI-related recommendations are made available to HRM based on the results of a statistical analysis.